The major genetic risk factor for severe Covid-19 is inherited from Neanderthals
nature.com
nature.com
https://www.telegraph.co.uk/news/2020/06/03/exclusive-corona...
A well engineered bioweapon would be a virus that goes undetected for a few months and then happens to kill the host due to complications. That can wipe out an entire country or possibly the whole human race. I don't think this is possible biologically.
All it needs is a long period when the host is contagious and asymptomatic. That way it spreads easily before killing the host.
> A well engineered bioweapon would be a virus that goes undetected for a few months and then happens to kill the host due to complications. That can wipe out an entire country or possibly the whole human race. I don't think this is possible biologically.
"Killing the host" is not some natural thing that happens with Viruses. It's a complex process of immune system + dosage. It's not like virus has any evolutionary interest in demobilizing the host. It goes against the evolutionary pressure. That's why I said "happens to kill the host", due to complications.
https://mumbaimirror.indiatimes.com/coronavirus/news/sero-su...
The highest genetic contribution to any common disease seems HLA-B27 ~ ankylosing spondylitis, closely followed by HLA II ~ type 1 diabetes. But in these cases, still, it just explains around 15% of the variance. After these big contributors, there's a long list of genes that contribute with exponentially diminishing effect sizes. And the overall contribution of genetics never exceeds 50%. It's good to understand some disease factors, but interventions are much simpler from the environmental side of things.
I'm surprised that COVID is not linked to HLA in any meaningful way. Probably the study from Pääbo is not accounting for HLA because of lack of imputed haplotypes. It's a bit of a statistics smell that there's no association whatsoever. Nothing shows up in his chr6 region in the Manhattan plot. All infectious agents have some correlation. That's the whole point of HLA, implementing different strategies against them.
For example, HLA-B57 and B27 tend to be super-responders against HIV. This haplotype seems to be trading more autoimmunity risk in exchange for better protection against rapidly mutating viruses. It expanded quite quickly around Northern Europe around 10000 years ago, probably due to another pandemic.
My HLA-B27 example was actually a positive one. It gives you higher chances of a good outcome if infected by HIV.
Another paper, with a small sample size, claims HLA-B44 and C01 are susceptible [1].
I work with the Oxford vaccine group, and I am quite interested in this effect, including in vaccinated patients. It's pretty well known bad vaccine efficiency and side effects will correlate very strongly with HLA, and with thymic involution.
Sadly everything is quite chaotic at the minute and it's difficult to get samples and funding for these ideas. If we were more advanced, we would get be classifying vulnerable patients and asking them to shield according to HLA and immunoageing/dysfunction markers.
So as I understand you are involved by the vaccine that AstraZeneca is also behind. So I kind of understand (well, as much as layman can understand, lol) the vaccine that Pfizer and Moderna works. I guess it is a bit better explained on Wikipedia. So their vaccines inject mRNA to our cells which start producing antibodies. While this is brand new kind of vaccine, it's hard to know long term effects of it, but there's a chance that it could cause an autoimmune disease.
When reading about vaccine created by Oxford, the biggest concern seems to be that people could have or develop antibodies for the adenovirus after first dose. I'm guessing someone with HLA-B27 has even a higher chance of doing that. I understand that, but I'm still not understanding how it works. Is it same as the mRNA vaccine, with the difference that the adenovirus is just used to deliver it?
The first issue is what you pointed out. Adenovirus delivery is potentially more risky. I'm incidentally also HLA-B27, and I will personally stay away from it.
The second issue, shared with all other vaccines, is that IMHO they should not have vaccinated us for the whole spike protein, but just for some fragment. The spike protein contains some mimotopes to confuse the immune system, and I'm worried that this might also be a source of autoimmunity in very rare cases. Naturally, because vaccines had to be rushed, this was not easy to account for.
Nonetheless, they all seem safe. Theoretically, mRNA ones might be safer, unless there's gene transfer/integration of mRNA into cells. But this is a very exotic issue unlikely to cause problems.
https://www.nature.com/articles/s41467-020-19623-x
(I'm not trying to be a jerk. I'm about to rush out the door, haven't had enough sleep and I think if we know something about what blood types are impacted, that's useful info.)
That press release does not give any actual numbers, but links to two studies. I quickly scanned the studies, so may have missed something, but the Denmark one seems to indicate a ~10% higher risk for A/AB than O. While statistically significant, it does not seem like a massive difference. Also, importantly, it states:
This study identifies ABO blood group as a risk factor for SARS-CoV-2 infection but not for hospitalization or death from COVID-19.
https://www.wikitree.com/g2g/1067199/new-clinical-study-link...
"A new genome-wide association study has identified a section of chromosome 3 where particular alleles are associated with severed effects after COVID_19 infection. This was then confirmed by a clinical trial of patients. The reported risk SNPs are having Cytosine (C) at position rs10490770 and Guanine (G) at rs35044562. These are in "full linkage disequilibrium", meaning if you have C at the first spot then you almost certainly have G at the second. And you can now check for C at rs10490770 in some 23andMe, Family Finder, and Ancestry raw data files, or directly on 23andMe using Browse Raw Data.
You can search for rs10490770 in your or other people's 23andMe v2,v3,v4, Family Finder and MyHeritage v1, or Ancestry v1,v2 raw data. It's not on the GSA chip, and therefore not on 23andMe v5, FTDNA v2, or MyHeritage v2. It is on Ancestry v1 and v2."
So you can search your 23andMe data for rs10490770 by going to https://you.23andme.com/tools/data/
More information and options are at https://customercare.23andme.com/hc/en-us/articles/115004310...
As a Bangladeshi now living outside of the country, I am not sure what to make of it. We didn't have any proper lockdown AFAIK. In a country with huge amount of poor populace, it's almost impossible to do mandate people to stay in home when they don't have means to live. Thus COVID is very widespread, although not reported because of lack of testing. Even with all that, COVID didn't cause much harm to the population. Albeit, all of it is ancedotal.
Rather than wasting many paragraphs talking about the Neanderthal connection, it would be vastly more useful to determine exactly what these genes do and why they are a risk factor for the disease.
The disease significantly impacts the blood. If we can determine, for example, what blood groups it impacts the worst, that might be meaningful -- a lot more meaningful than "There's a Neanderthal connection."
Beyond that, I don't know and don't care about that end of things, really. I'm much more interested in this end of things where I have a smidgen of influence -- that being "What do we see as a priority in discussing the problem on HN?" because HN attracts a lot of brilliant and connected people, so I imagine if we come up with a better mental model for solving the problem here, it will proliferate.
Besides, where do you get the idea that getting funded to work on the Neanderthal genome is easier than getting funded to work on an ongoing pandemic? Not that Pääbo needs it, as a Max Planck director he doesn't need to apply for grants.
What's happening here is simply that the world's Neanderthal genome experts continue working on Neanderthal genomes, and when they find something that is related to the pandemic it ends up in Nature and the popular press.
I stated as clearly as I know how that it is my general understanding, not specific to this article or what is being studied here.
I get the idea from my sister who worked at the CDC for many years and also had multiple rounds of cancer. And before life got in the way and she and I stopped being able to hang on the phone regularly, she used to routinely read the latest cancer research because she worked at the CDC and because she had cancer.
And she used to routinely bitch to me about how "98 percent of it is some variation on the same thing because it's what is trendy and it's what you can readily get funding for. There's almost nothing actually new and interesting in breast cancer research."
She was also patient zero in a cutting edge study and yadda. She was very much an insider in multiple ways and she and I were close at one time, before I was homeless and had no phone for a year or more and before she began working 16 hours a day and had no time talk to anyone regularly, not even our mother.
If someone prefers their papers as PDFs, there is also one available on the website (I for one hate the mess that these "web papers" are): https://www.nature.com/articles/s41586-020-2818-3.pdf
[0] "A recent genetic association study identified a gene cluster on chromosome 3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative)2 comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization."
[1] "Here we show that the risk is conferred by a genomic segment of around 50 kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe."
For this research - just because you've identified a gene linked to risk, doesn't mean you can say anything about why or how that happens. We likely don't know much about this area of the genome - how it's expressed, etc. and so they went with the angle we DID know - that it's inherited from neanderthal. No doubt more research in this area will be done now that they've found a region of interest.
If anyone can cast some light on what chromosome 3 does, that would be cool. (Maybe it's in the article and bad eyesight plus lack of sleep is causing me to miss it?)
My main point was just: What do these genes actually do in the body? We should be looking at that. It's a much more important question than where these genes come from.
The sentence following your quote says a new study suggests genes determining blood groups are NOT associated with COVID severity. If you want to criticize the paper, at least quote something that the paper actually supports. As to your main point, others are working on the functional part. The authors just report a finding with their expertise. Not every scientific paper immediately solves a practical problem.
There is no claim here of a novel finding of immediate biomedical significance; rather this builds on top of other people's biomedically relevant work, which is cited in the abstract.
When the pandemic started, there were numerous articles on the front page of HN about ventilators and how to build your own and nonsense like that and I was critical of that as well. And it soon turned out that ventilators weren't really a good solution.
Neanderthal experts can study whatever they want to study, but their research is being connected to this pandemic and given that we are in lock down number two, I think we have more urgent issues than where these genes came from and I wish people in general -- the world at large -- would focus on that.
Granted, I'm short of sleep and no doubt saying things somewhat ham-handedly.
I got better by looking at what we know about how the genetic defect impacts cell function in my body and learning a lot about cell function and connecting the dots between the micro -- molecules misprocessed at the cellular level -- and the macro -- dysfunction in certain tissues and how the body handles and mishandles food, among other things.
I'm not capable of setting aside twenty years of life experience in order to fit myself neatly into the Overton Window, especially when short of sleep.
It never ceases to amaze me how much negative attention my comments get, like it's just incredibly important for people who think they know more about science than I do to quash my ability to give my 2 cents.
My stellar credentials include being a homemaker for two decades and spending nearly six years homeless. Everyone on the planet is more than welcome to look at my comments, decide quietly to themselves that I'm an idiot who knows nothing, downvote it and move the fuck on rather than lecturing me about the crime of having thoughts about the pandemic and what I think we should be looking at if we actually want to solve it and not treat it like we are looky-loos at a zoo seeking entertainment in the deaths of our fellow human beings.
Science also includes critical thinking, critique of what has been done, rigorous discussion and a whole lot of other things beyond just dicking around with exploring whatever catches our fancy for funsies.
It seems like you have some resentment because you don't feel your personally acquired knowledge is being valued correctly? That may be the case generally, but it's not the case here, I assure you.
It’s the modern era’s equivalent of musicians and artists courting wealthy patrons, in order to keep funding flowing.
Black holes, Dinosaurs, Neanderthals, ...
Racism and inequality are awful.
That brings to mind a naming question.
Most researchers seem to put the identical ancestors point (also known as the all common ancestors point or the genetic isopoint) for humans at somewhere in the last 20k years.
That's the point where every single human alive either had no descendants who are alive today or everyone alive today is their descendant.
Since the Neanderthals were extinct long before the identical ancestor point, it follows that if anyone alive today is descended from Neanderthals, then everyone alive today is descended from Neanderthals.
The naming question: is there a word or term for when person A is a descendant of person B but does not have any genes from B?
I've heard of someone using the term "homeopathic descendant" for this, but I think that was offered as a joke.
> that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe.
(I have a red beard and 23andme confirmed my Neanderthal genes)
I'm not personally against identifying physical traits that would help serve as a quick-and-dirty visual test of risk assessment and I don't know what's going on with downvotes on HN beyond "there's a pandemic on and voting has been wonky all year, presumably because people are stressed out."
When I was getting divorced, I did not want to date men who were likely to be carriers because it's homozygous recessive, so if the father is a carrier there is a 50 percent chance the child will be a carrier and a 50 percent chance they will have CF. I am incapable of producing a "normal" child (and didn't know that when I was having kids).
My quick and dirty genetics test to drastically reduce the odds that I was dating a carrier boiled down to "No White Men Allowed." Other ethnicities are dramatically less likely to be carriers.
So it doesn't sound silly to me at all that you could take one look at someone and infer some stats about the odds of their genetic risks for a specific category.
I have a predominantly Caucasian genetic disorder. The quick-and-dirty visual test for "How high is your risk of being a carrier or having the condition?" is "Are you White?"